A critical influence of HIF-1 on MMP-9 and Galectin-3 in oral lichen planus.

OBJECTIVE: Oral lichen planus carries a risk for malignancy. The pathogenesis of the disease is mediated by various inflammatory mediators. Several mediators could be responsible for the oncogenic behavior in certain cases. Hypoxia-inducible factor-1a (HIF-1), and its possible correlation to Galactin-3 (Gal-3) and matrix metalloproteinase-9 (MMP-9) over expression represents an important indicator for malignant transformation. The investigation of these factors may present evidence-based information on malignant transformation of the disease. SUBJECTS AND METHODS: The study investigated the expression of HIF-1, Gla-3 and MMP-9 in tissue samples of OLP compared to control subjects of un-inflamed gingival overgrowth. 20 biospecimen were allocated in each group. RESULTS: Immunohistochemical findings of OLP showed immunoreactivity for Galectin 3, HIF1a and MMP-9 by most of the epithelial cells. There was a positive correlation between HIF1α and MMP-9, r = 0.9301 (P-value < 0.00001). A positive correlation was detected between Galectin 3 and MMP-9, r = 0.7292 (P-value = 0.000264) between Galectin 3 and HIF1α, r = 0.5893 (P-value = 0.006252). CONCLUSION: These findings confirm the hypothesis that the adaptive pathways to hypoxia as Gal 3 and MMP-9 expressions and their HIF-1 may play a crucial role in carcinogenesis of OLP.

Evaluation of Immediate Implants Augmented with Autogenous Bone/Melatonin Composite Graft in the Esthetic Zone: A Randomized Controlled Trial.

PURPOSE: To evaluate the clinical and radiographic outcomes following the application of autogenous bone (ABG)/melatonin composite graft around immediate implants in the esthetic zone compared to ABG alone. MATERIALS AND METHODS: Twenty-six patients with two nonrestorable anterior/premolar teeth were randomly classified into two equal groups. Dental implants were immediately inserted either with ABG (control group) or ABG/melatonin (test group). Outcome measures were peri-implant sulcus depth (PD), gingival index (GI), and wound healing scores. Cone beam computed tomography (CBCT) was recorded at baseline, 6, and 9 months. RESULTS: At the end of the study, a significant difference was shown in the mean of marginal bone loss between the control group (1.91 mm ± 0.42) and the test group (0.84 mm ± 0.34) at p = 0.0001. The test group showed a significant gain in bone density, 500.73 ± 40.92, versus 420.14 ± 38.33 in the control group (p = 0.0001). There was a statistically significant difference between the control group (0.68 ± 0.42) versus the test group (0.45 ± 0.49; p = 0.044) in GI. PD was significantly reduced at the end of the study in the test group (0.42 mm ± 0.50; p = 0.002), with a similar significant improvement in the healing scores (p = 0.026). CONCLUSION: Within the limitations of this study, immediate implants augmented with ABG/melatonin composite graft would be a valuable option in the esthetic zone.

Expression of CD163 in hereditary gingival fibromatosis: A possible association with TGF-ß1.

BACKGROUND: Although several studies have discussed some of the molecular and cellular changes associated with hereditary gingival fibromatosis (HGF), its pathogenesis is still largely unclear. This study was directed to detect and outline the degree of relationship between the immunophenotyped macrophages (M2) expressing CD163 and TGF-ß1 in patients with gingival overgrowth due to HGF. METHODS: Biopsies from 20 patients suffering from HGF and 20 normal control subjects were harvested, histologically and immunohistochemically stained then, analyzed and statistically compared and correlated for CD163 immunoexpression and TGF-ß1. RESULTS: All HGF specimens expressed TGF-ß1 by most of the connective tissue fibroblasts, with statistically high significant mean of area % (2.61 ± 0.41) compared to normal controls (0.11 ± 0.06; P = .001). All control specimens revealed negligible CD163 immunostaining of the few inflammatory cells found with a mean area of % (0.69 ± 0.12), while the specimens of HGF cases showed statistically significant higher CD163 expression (3.39 ± 0.75) at (P = .007). A statistically significant higher mean % of M2 cells expressing CD163 in relation to the total number of the inflammatory cells was revealed in HGF (34.46 ± 2.04) compared to the control group (16.36 ± 2.39; P-value ≤ .05). Moderate correlation between CD163 and TGF-ß1 was detected in HGF (r = .451; P-value < .05). CONCLUSIONS: CD163 and TGF-ß1 were clearly expressed in HGF cases compared to healthy control patients, with significant correlation. In HGF, the increase in CD 163-positive cells was specific and not dependent on the chronic gingival inflammation.

ALK1 expression in oral lichen planus: a possible relation to microvessel density.

OBJECTIVE: To assess the expression of activin receptor-like kinase 1 (ALK1) and investigate its possible relationship with microvessel density (MVD) in different forms of oral lichen planus (OLP) compared to controls' biopsies. METHODS: Biopsies from 20 reticular/papular OLP (R/PLP), 20 atrophic/erosive OLP (A/ELP) patients, and 20 healthy subjects were immunohistochemically analyzed and statistically compared and correlated for ALK1 expression and MVD as assessed by CD34 expression. RESULTS: All OLP specimens revealed the presence of positive cytoplasmic CD34 immunostaining in endothelial cells, with statistically high significant MVD in each of R/PLP (Median; M = 4.40) and A/ELP (M = 7.69) compared to controls (M = 1.16) (P < 0.001). Statistically significant MVD was found in A/ELP compared to R/PLP (P < 0.001). All control specimens revealed negative ALK1 immunostaining of the few inflammatory cells found, while 85% of A/ELP cases and 70% of R/PLP cases showed positively immunostained sections for ALK-1, with statistically significant higher ALK1 expression In A/ELP (M = 1.95) compared to R/PLP (M = 0.86) (P = 0.005). No significant correlation between CD34 and ALK1 was detected in R/PLP (r = 0.081), while a barely moderate positive correlation was found in A/ELP (r = 0.396). CONCLUSIONS: ALK1 expression and MVD are increased in OLP, particularly in A/ELP type.

A Novel Surgical Approach for Treatment of Class II Furcation Defects Using Marginal Periosteal Membrane.

OBJECTIVES: This study was designed to describe and evaluate the use of a vascularized marginal periosteal barrier membrane (MPM) harvested by a semilunar incision, alone or combined with a bone graft, in treatment of class II furcation defects in mandibular molars, compared to open flap debridement (OFD). METHODS: Thirty class II furcation defects in mandibular molars were randomly assigned into three equal groups: Group I included OFD, Group II included defects treated with MPM, and Group III consisted of defects treated with MPM after applying demineralized freeze-dried bone allograft (DFDBA). At baseline and 6-month follow-up, vertical probing depth (VPD), clinical attachment level (CAL) measurements, along with a radiographic measurement of bone height (BH), were obtained for each defect. Transmission electron microscopy (TEM) was used for further evaluation of the histological changes associated with gingival samples related to each line of treatment. RESULTS: Both Groups II and III reflected significant favorable outcomes in all the assessed parameters compared to OFD. A non-significant difference was found between both groups regarding VPD, while significant improvement in CAL and BH were detected in Group III (p ≤ 0.05). Favorable histological findings were also noticed in the test groups, with more improvement in Group III. CONCLUSION: Placement of a vascularized MPM as a barrier membrane, using a semilunar incision, demonstrated a significant improvement in both clinical and histological outcomes of class II furcation defects in lower molars. When it was combined with DFDBA, a meaningful difference was found with regard to early wound healing and gain in CAL and BH.

IL-18 gene polymorphisms in aphthous stomatitis vs. Behçet's disease in a cohort of Egyptian patients.

OBJECTIVE: A clinical investigation of the potential correlation of two single-nucleotide polymorphisms at -137 (G/C) and -607 (C/A) in the promoter region of the IL-18 gene, with the susceptibility to aphthous stomatitis and Behçet's disease. PATIENT AND METHODS: This study included 80 aphthous stomatitis patients and 80 patients with Behçet's disease. Eighty healthy subjects were enrolled as a control group. IL-18 single-nucleotide polymorphisms at -607 and -137 regions were analyzed using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The genotype and allele distributions of the two regions did not differ significantly between patients with aphthous stomatitis and controls. The genotype and allele distributions at -607 were significantly different between patients with Behçet's disease [CC (P = 0.044), C allele (P = 0.043), A allele (P = 0.043)], and controls. The frequency of the GG genotype at position -137 in patients with Behçet's disease was associated only with a higher rate of ocular manifestations (OR= 1.4, CI= 0.76-2.7, P = 0.031). CONCLUSION: IL-18 gene polymorphisms were not associated with any susceptibility to aphthous stomatitis, while a positive association was found with patients with Behçet's disease regarding -607 promoter site. Moreover, patients with Behçet's disease carrying the GG genotype at position -137 had a higher risk of developing ocular manifestations.

Use of Melatonin/Decorticotomy and Autogenous Bone Graft in Induced 1-Wall Defect.

PURPOSE: This study was designed to investigate the effect of intramarrow penetration (IMP) and 1% melatonin (MLN) gel on the remodelling process of autogenous bone graft (ABG) in an induced 1-osseous wall defect model. METHODS: Sixty-four intrabony induced mandibular defects were created on the distal side of premolars-P1, P2, P3, and P4 (on each side)-in 8 beagle dogs. A ligature-induced periodontitis was initiated in each defect. Defects were then divided into 4 equal groups. Group I was treated with open-flap debridement (OFD) alone, group II was treated with OFD/ABG, group III was treated with OFD/IMP/ABG, and group IV was treated with OFD/ABG/IMP/1% MLN gel. The study parameters were bone fill, histologic analysis, and immunohistochemical evaluation of endothelial nitric oxide synthase (eNOS) expression at 2-week (2W) and 8-week (8W) time intervals. RESULTS: At 8W, significant differences were revealed amongst all groups regarding the amount of bone fill and eNOS expressions (P < .001). Bone fill percentages were 55.5%, 22.3%, 16.8%, and 0% in groups IV, III, II, and I, respectively. eNOS expressions were 1.68 ± 0.06, 8.43 ± 0.04, 16.80 ± 0.17, and 1.97 ± 0.07 in groups IV, III, II, and I, respectively. The favourable results were in line with group IV. CONCLUSIONS: According to these preliminary results, defects treated by ABG augmented with IMP and 1% MLN gel revealed a greater amount of bone fill and reduced eNOS expression. This combination is therefore highly suggested as an adjunct to ABG.

Topical pimecrolimus effect on Fas inducing apoptosis in oral lichen planus: a clinical immunohistochemical study.

OBJECTIVE: To investigate the effectiveness of pimecrolimus treatment in patients not responding to corticosteroid treatment and to investigate its effect on Fas expression on keratinocytes in oral lichen planus (OLP). SUBJECTS AND METHODS: Twenty patients with OLP were recruited from the Oral Medicine Clinic at the School of Dentistry, Ain Shams University, Egypt. Pimecrolimus 1% cream with a hydrophilic adhesive gel base was applied to the oral lesions, four times daily, for a total of 2 months. A marker lesion was identified and assessed by clinical scoring (CS). The symptomatology score was obtained using a visual analog scale (VAS). Pre-treatment and post-treatment specimens were immunohistochemically stained for detecting Fas. RESULTS: The results of clinical scores showed statistically high significant improvement (P = 0.0001). The mean VAS decreased significantly over time as well as the mean of Fas expression (P < 0.05). The overall percentage of reduction from baseline to week 8 was 87%, 93%, and 67% for clinical scores, visual analog score, and Fas expression, respectively. CONCLUSIONS: Topical pimecrolimus reduced Fas expression, and it appears to be a promising alternative treatment for OLP.

Correlation of VEGF and MMP-2 levels in oral lichen planus: An in vivo immunohistochemical study.

BACKGROUND: This study aimed to investigate the relation between vascular endothelial growth factors (VEGF) and matrix metalloproteinase-2 (MMP-2) in different oral lichen planus (OLP) forms compared to control patients. METHODS: Biopsies from 60 patients were selected and equally distributed as follows: reticular/popular OLP (R/PLP), atrophic/erosive OLP (A/ELP) patients, healthy subjects (Control). All biopsies were immune-histochemical stained and statistically analyzed for VEGF and MMP-2 expression. RESULTS: Immune-expression of VEGF was significant between OLP and control (P-value <0.001). OLP showed a higher epithelial expression of VEGF in A/ELP compared to R/PLP (15.19 ± 2.53). In connective tissue (CT), R/PLP showed a higher VEGF expression (11.57 ± 2.32) compared to A/ELP (9.87 ± 2.48); (p < 0.001), with no significant difference (P-value ≥ 0.05). A significant epithelial expression of MMP-2 was seen in A/ELP compared to R/PLP (21.32 ± 7.08). R/PLP showed a higher expression of MMP-2 (20.45 ± 6.28) in CT compared to A/ELP group (17.66 ± 6.94), with a non-significant difference (P-value = 1.000). In A/ELP, a positive correlation between VEGF and MMP-2 was detected in CT, r = 0.761, with a weak correlation was noticed in epithelium r = 0.163. A negative correlation was noted between VEGF and MMP-2 in R/PLP in CT, r = -0.368, with a moderate positive correlation in epithelium, r = 0.655. CONCLUSION: MMP-2 and VEGF protein profiles support a role in the pathogenesis of OLP. Based the MMP-2 and VEGF findings in the A/ELP group, this pathway may have a role in the malignant transformation of these lesions. Both observations invite further study.

Evaluation of Adjunctive Use of Low-Level Diode Laser Biostimulation with Combined Orthodontic Regenerative Therapy.

BACKGROUND: The combined orthodontic regenerative therapy approach can greatly enhance periodontal conditions and dentofacial aesthetics in many situations. The purpose of this study was to evaluate the effectiveness of 940nm low-level diode laser biostimulation in enhancement of intrabony wound healing with combined orthodontic/regenerative therapy in chronic periodontitis subjects suffering from malocclusion. METHODS: Fifteen chronic periodontitis adult patients with at least two intrabony defects and requiring orthodontic treatment for abnormalities in occlusion were included. A total of 30 defects were divided into two groups and treated in a split mouth design. The defects were treated with combined orthodontic regenerative therapy with laser irradiation (Group I: test group) or with combined orthodontic regenerative therapy alone (Group II: control group). The following hard and soft tissue measurements were recorded at baseline (prior to surgery) and after six and nine months postoperatively: probing depth (PD), clinical attachment level (CAL) by periodontal calibrated probe and bone density (BD) using the DBS-Win software. RESULTS: Probing depth reduction was 64.57%±9.37 and 64.95%±10.07 with no statistically significant difference between Group I and Group II. Percent change in clinical attachment level gain were 59.77%±12.107and 38.83%±7.56 in Group I and II respectively, with a statistically signifi cant difference (P-value =0.005considered signifi cant). Moreover, defects treated with combined orthodontic regenerative therapy with laser irradiation showed signifi cant preservation of bone density with a percent decrease of 4.14%±3.17 at the end of the study period. CONCLUSION: Improvements in clinical and radiographic parameters were observed following the adjunctive use of low-level diode laser therapy and orthodontic regenerative therapy for the management of intrabony defects in chronic periodontitis patients.

A Randomized Placebo-Controlled Intervention with ß-Glucan in the Treatment of Localized Aggressive Periodontitis.

BACKGROUND AND OBJECTIVES: The success of any surgical procedure is predominately influenced by the pattern of its wound healing. The objective of the present study was to assess gingival crevicular fluid (GCF) and serum matrix metalloproteinase-8 (MMP-8) levels during the early healing phase of root coverage procedures. MMP-8 levels on days four and seven were correlated with the wound healing index (WHI) to evaluate the presence of MMP-8 during early post-surgical wound healing after root coverage procedures. MATERIALS AND METHODS: Fifteen isolated maxillary Miller's Class I/Class II recession defects in systemically and periodontally healthy patients in the age range of 25 - 57 years were treated with coronally advanced flap and sub-epithelial connective tissue graft (CAF + SCTG). GCF and serum samples were collected at baseline, day four, day seven and six months after surgery from the gingival sulcus of the recession defect. A contralateral tooth with clinically healthy gingiva was used as control and samples were collected from this site too at the same time intervals. MMP-8 levels in GCF and serum were measured using enzyme-linked immunosorbent assay (ELISA). Wound Healing Index was assessed on days four and seven. Mean root coverage (MRC) and complete root coverage (CRC) were assessed six months post-operatively. RESULTS: Statistically signifi cant reduction in recession depth was observed with MRC of 88.67%. GCF and serum MMP-8 levels were significantly elevated on days four and seven post-surgery (p less than 0.001) in the test site and reduced to baseline levels after six months. Weak positive correlation was observed between wound healing index and GCF MMP-8 levels on days four and seven. Moderate positive correlation was noted between serum MMP-8 levels and root coverage outcomes. However, this correlation was not statistically signifi cant (p greater than 0.05). CONCLUSION: The present prospective study showed satisfactory post-surgical healing and root coverage outcome. MMP-8 levels and its increase/decrease during the early wound healing follows the expected temporal pattern. No significant correlation was noted between MMP-8 levels during early wound healing and root coverage outcomes.